Subvenite

Serious warning

The strongest warning the FDA requires. It is printed in a box at the top of the label.

Quoted from the official label, section “Boxed Warning”.

Do not take it if

Quoted from the official label, section “Contraindications”.

How to take it

These directions are for this exact strength and form. Another one is different.

• Dosing is based on concomitant medications, indication, and patient age.
• ( 2.1 , 2.2 , 2.3 , 2.4 ) To
• avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations should not be exceeded.
• SUBVENITE Starter Kits are available for the first 5 weeks of treatment.
• ( 2.1 , 16 ) Do not restart SUBVENITE in patients who discontinued due to rash unless the potential benefits clearly outweigh the risks.
• ( 2.1 , 5.1 ) Adjustments to maintenance doses will be necessary in most patients starting or stopping estrogen-containing products, including oral contraceptives.
• ( 2.1 , 5.9 ) Discontinuation:
• Taper over a period of at least 2 weeks (approximately 50% dose reduction per week).
• ( 2.1 , 5.10 ) Epilepsy:
• Adjunctive therapy—See Table 1 for patients older than 12 years and Tables 2 and 3 for patients aged 2 to 12 years.
• ( 2.2 ) Conversion to monotherapy—See Table 4.
• ( 2.3 ) Bipolar disorder: See Tables 5 and 6.
• ( 2.4 )
• 2.1 General Dosing Considerations Rash There are suggestions that the risk of severe, potentially life-threatening rash may be increased by (1) coadministration of SUBVENITE with valproate, (2) exceeding the recommended initial dose of SUBVENITE, or (3) exceeding the recommended dose escalation for SUBVENITE.
• However, cases have occurred in the absence of these factors [see Boxed Warning ].
• Therefore, it is important that the dosing recommendations be followed closely.
• The risk of nonserious rash may be increased when the recommended initial dose and/or the rate of dose escalation for SUBVENITE is exceeded and in patients with a history of allergy or rash to other AEDs.
• SUBVENITE Starter Kits provide SUBVENITE at doses consistent with the recommended titration schedule for the first 5 weeks of treatment, based upon concomitant medications, for patients with epilepsy (older than 12 years) and bipolar I disorder (adults) and are intended to help reduce the potential for rash.
• The use of SUBVENITE Starter Kits is recommended for appropriate patients who are starting or restarting SUBVENITE [see How Supplied/Storage and Handling ( 16 )] .
• It is recommended that SUBVENITE not be restarted in patients who discontinued due to rash associated with prior treatment with lamotrigine unless the potential benefits clearly outweigh the risks.
• If the decision is made to restart a patient who has discontinued SUBVENITE, the need to restart with the initial dosing recommendations should be assessed.
• The greater the interval of time since the previous dose, the greater consideration should be given to restarting with the initial dosing recommendations.
• If a patient has discontinued lamotrigine for a period of more than 5 half-lives, it is recommended that initial dosing recommendations and guidelines be followed.
• The half-life of lamotrigine is affected by other concomitant medications [see Clinical Pharmacology ( 12.3 )].
• SUBVENITE Added to Drugs Known to Induce or Inhibit Glucuronidation Because lamotrigine is metabolized predominantly by glucuronic acid conjugation, drugs that are known to induce or inhibit glucuronidation may affect the apparent clearance of lamotrigine.
• Drugs that induce glucuronidation include carbamazepine, phenytoin, phenobarbital, primidone, rifampin, estrogen-containing products, including oral contraceptives, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir.
• Valproate inhibits glucuronidation.
• For dosing considerations for SUBVENITE in patients on estrogen-containing products, including contraceptives, and atazanavir/ritonavir, see below and Table 13.
• For dosing considerations for SUBVENITE in patients on other drugs known to induce or inhibit glucuronidation, see Tables 1, 2, 5 to 6, and 13.
• Target Plasma Levels for Patients with Epilepsy or Bipolar Disorder A therapeutic plasma concentration range has not been established for lamotrigine.
• Dosing of SUBVENITE should be based on therapeutic response [see Clinical Pharmacology ( 12.3 )].
• Women Taking Estrogen-Containing Oral Contraceptives Starting SUBVENITE in Women Taking Estrogen-Containing Oral Contraceptives:
• Although estrogen-containing oral contraceptives have been shown to increase the clearance of lamotrigine , no adjustments to the recommended dose-escalation guidelines for SUBVENITE should be necessary solely based on the use of estrogen-containing oral contraceptives [see Clinical Pharmacology ( 12.3 )] .
• Therefore, dose escalation should follow the recommended guidelines for initiating adjunctive therapy with SUBVENITE based on the concomitant AED or other concomitant medications (see Tables 1, 5, and 7).
• See below for adjustments to maintenance doses of SUBVENITE in women taking estrogen-containing oral contraceptives.
• Adjustments to the Maintenance Dose of SUBVENITE in Women Taking Estrogen-Containing Oral Contraceptives:
• (1) Taking Estrogen-Containing Oral Contraceptives:
• In women not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation, the maintenance dose of SUBVENITE will in most cases need to be increased by as much as 2-fold over the recommended target maintenance dose to maintain a consistent lamotrigine plasma level [see Drug Interactions (7), Clinical Pharmacology ( 12.3 )] .
• (2) Starting Estrogen-Containing Oral Contraceptives:
• In women taking a stable dose of SUBVENITE and not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation, the maintenance dose will in most cases need to be increased by as much as 2-fold to maintain a consistent lamotrigine plasma level [see Drug Interactions (7), Clinical Pharmacology ( 12.3 )] .
• The dose increases should begin at the same time that the oral contraceptive is introduced and continue, based on clinical response, no more rapidly than 50 to 100 mg/day every week.
• Dose increases should not exceed the recommended rate (see Tables 1 and 5) unless lamotrigine plasma levels or clinical response support larger increases.
• Gradual transient increases in lamotrigine plasma levels may occur during the week of inactive hormonal preparation (pill-free week), and these increases will be greater if dose increases are made in the days before or during the week of inactive hormonal preparation.
• Increased lamotrigine plasma levels could result in additional adverse reactions, such as dizziness, ataxia, and diplopia.
• If adverse reactions attributable to SUBVENITE consistently occur during the pill-free week, dose adjustments to the overall maintenance dose may be necessary.
• Dose adjustments limited to the pill-free week are not recommended.
• For women taking SUBVENITE in addition to carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation, no adjustment to the dose of SUBVENITE should be necessary [see Drug Interactions ( 7 ), Clinical Pharmacology ( 12.3 )] .
• (3) Stopping Estrogen-Containing Oral Contraceptives:
• In women not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation, the maintenance dose of SUBVENITE will in most cases need to be decreased by as much as 50% in order to maintain a consistent lamotrigine plasma level [see Drug Interactions (7), Clinical Pharmacology ( 12.3 )] .
• The decrease in dose of SUBVENITE should not exceed 25% of the total daily dose per week over a 2-week period, unless clinical response or lamotrigine plasma levels indicate otherwise [see Clinical Pharmacology ( 12.3 )] .
• In women taking SUBVENITE in addition to carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation, no adjustment to the dose of SUBVENITE should be necessary [see Drug Interactions (7), Clinical Pharmacology ( 12.3 )] Women and Other Hormonal Contraceptive Preparations or Hormone Replacement Therapy The effect of other hormonal contraceptive preparations or hormone replacement therapy (HRT) on the pharmacokinetics of lamotrigine has not been systematically evaluated.
• Other estrogen-containing therapies, such as HRT, may interfere with lamotrigine.
• Therefore, close clinical monitoring on effectiveness of SUBVENITE with dose adjustment may be necessary [see Warnings and Precautions ( 5.9 )] .
• It has been reported that ethinylestradiol, not progestogens, increased the clearance of lamotrigine up to 2-fold, and the progestin-only pills had no effect on lamotrigine plasma levels.
• Therefore, adjustments to the dosage of SUBVENITE in the presence of progestogens alone will likely not be needed.
• Patients Taking Atazanavir/Ritonavir While atazanavir/ritonavir does reduce the lamotrigine plasma concentration, no adjustments to the recommended dose-escalation guidelines for SUBVENITE should be necessary solely based on the use of atazanavir/ritonavir.
• Dose escalation should follow the recommended guidelines for initiating adjunctive therapy with SUBVENITE based on concomitant AED or other concomitant medications (see Tables 1, 2, and 5).
• In patients already taking maintenance doses of SUBVENITE and not taking glucuronidation inducers, the dose of SUBVENITE may need to be increased if atazanavir/ritonavir is added or decreased if atazanavir/ritonavir is discontinued [see Clinical Pharmacology ( 12.3 )] .
• Patients with Hepatic Impairment Experience in patients with hepatic impairment is limited.
• Based on a clinical pharmacology study in 24 subjects with mild, moderate, and severe liver impairment , the following general recommendations can be made [see Use in Specific Populations (8.6), Clinical Pharmacology ( 12.3 )] .
• No dosage adjustment is needed in patients with mild liver impairment.
• Initial, escalation, and maintenance doses should generally be reduced by approximately 25% in patients with moderate and severe liver impairment without ascites and 50% in patients with severe liver impairment with ascites.
• Escalation and maintenance doses may be adjusted according to clinical response.
• Patients with Renal Impairment Initial doses of SUBVENITE should be based on patients' concomitant medications (see Tables 1 to 3 and 5); reduced maintenance doses may be effective for patients with significant renal impairment [see Use in Specific Populations ( 8.7 ), Clinical Pharmacology ( 12.3 )].
• Few patients with severe renal impairment have been evaluated during chronic treatment with SUBVENITE.
• Because there is inadequate experience in this population, SUBVENITE should be used with caution in these patients.
• Discontinuation Strategy Epilepsy:
• For patients receiving SUBVENITE in combination with other AEDs, a re-evaluation of all AEDs in the regimen should be considered if a change in seizure control or an appearance or worsening of adverse reactions is observed.
• If a decision is made to discontinue therapy with SUBVENITE, a step-wise reduction of dose over at least 2 weeks (approximately 50% per week) is recommended unless safety concerns require a more rapid withdrawal [see Warnings and Precautions ( 5.10 )].
• Discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation should prolong the half-life of lamotrigine; discontinuing valproate should shorten the half-life of lamotrigine.
• Bipolar Disorder:
• In the controlled clinical trials, there was no increase in the incidence, type, or severity of adverse reactions following abrupt termination of SUBVENITE.
• In the clinical development program in
• adults with bipolar disorder, 2 patients experienced seizures shortly after abrupt withdrawal of SUBVENITE.
• Discontinuation of SUBVENITE should involve a step-wise reduction of dose over at least 2 weeks (approximately 50% per week) unless safety concerns require a more rapid withdrawal [see Warnings and Precautions ( 5.10 )] .
• 2.2 Epilepsy-Adjunctive Therapy This section provides specific dosing recommendations for patients older than 12 years and patients aged 2 to 12 years.
• Within each of these age-groups, specific dosing recommendations are provided depending upon concomitant AEDs or other concomitant medications (see Table 1 for patients older than 12 years and Table 2 for patients aged 2 to 12 years).
• A weight-based dosing guide for patients aged 2 to 12 years on concomitant valproate is provided in Table 3.
• Patients Older than 12 Years Recommended dosing guidelines are summarized in Table 1.
• Table 1.
• Escalation Regimen for SUBVENITE in Patients Older than 12 Years with Epilepsy In Patients TAKING Valproate a In Patients NOT TAKING Carbamazepine , Phenytoin , Phenobarbital , Primidone b , or Valproate a In Patients TAKING Carbamazepine , Phenytoin , Phenobarbital , or Primidone b and NOT TAKING Valproate a Weeks 1 and 2 25 mg every other day 25 mg every day 50 mg / day Weeks 3 and 4 25 mg every day 50 mg / day 100 mg / day (in 2 divided doses) Week 5 onward to maintenance Increase by 25 to 50 mg/day every 1 to 2 weeks.
• Increase by 50 mg/day every 1 to 2 weeks.
• Increase by 100 mg/day every 1 to 2 weeks.
• Usual maintenance dose 100 to 200 mg / day with valproate alone 100 to 400 mg / day with valproate and other drugs that induce glucuronidation (in 1 or 2 divided doses) 225 to 375 mg / day (in 2 divided doses) 300 to 500 mg / day (in 2 divided doses) a Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions ( 7 ), Clinical Pharmacology ( 12.3 )]. b Drugs that induce lamotrigine glucuronidation and increase clearance, other than the specified AEDs, include estrogen-containing oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir.
• Dosing recommendations for estrogen-containing products, including oral contraceptives, and the protease inhibitor atazanavir/ritonavir can be found in General Dosing Considerations [see Dosage and Administration ( 2.1 )] .
• Patients on rifampin and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with AEDs that induce glucuronidation and increase clearance [see Dosage and Administration ( 2.1 ), Drug Interactions ( 7), Clinical Pharmacology ( 12.3 )].
• Patients Aged 2 to 12 Years Recommended dosing guidelines are summarized in Table 2.
• Lower starting doses and slower dose escalations than those used in clinical trials are recommended because of the suggestion that the risk of rash may be decreased by lower starting doses and slower dose escalations.
• Therefore, maintenance doses will take longer to reach in clinical practice than in clinical trials.
• It may take several weeks to months to achieve an individualized maintenance dose.
• Maintenance doses in patients weighing <30 kg, regardless of age or concomitant AED, may need to be increased as much as 50%, based on clinical response.
• Table 2.
• Escalation Regimen for SUBVENITE in Patients Aged 2 to 12 Years with Epilepsy In Patients TAKING Valproate a In Patients NOT TAKING Carbamazepine , Phenytoin , Phenobarbital , Primidone b , or Valproate a In Patients TAKING Carbamazepine , Phenytoin , Phenobarbital , or Primidone b and NOT TAKING Valproate a Weeks 1 and 2 0 . 15 mg / kg / day in 1 or 2 divided doses, rounded down to the nearest whole tablet (see Table 3 for weight-based dosing guide) 0 . 3 mg / kg / day in 1 or 2 divided doses, rounded down to the nearest whole tablet 0 . 6 mg / kg / day in 2 divided doses, rounded down to the nearest whole tablet Weeks 3 and 4 0 . 3 mg / kg / day in 1 or 2 divided doses, rounded down to the nearest whole tablet (see Table 3 for weight-based dosing guide) 0 . 6 mg / kg / day in 2 divided doses, rounded down to the nearest whole tablet 1 . 2 mg / kg / day in 2 divided doses, rounded down to the nearest whole tablet Week 5 onward to maintenance The dose should be increased every 1 to 2 weeks as follows:
• calculate 0.3 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose.
• The dose should be increased every 1 to 2 weeks as follows:
• calculate 0.6 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose.
• The dose should be increased every 1 to 2 weeks as follows:
• calculate 1.2 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose.
• Usual maintenance dose 1 to 5 mg / kg / day (maximum 200 mg/day in 1 or 2 divided doses) 1 to 3 mg / kg / day with valproate alone 4 . 5 to 7 . 5 mg / kg / day (maximum 300 mg/day in 2 divided doses) 5 to 15 mg / kg / day (maximum 400 mg/day in 2 divided doses) Maintenance dose in patients <30 kg May need to be increased by as much as 50%, based on clinical response.
• May need to be increased by as much as 50%, based on clinical response.
• May need to be increased by as much as 50%, based on clinical response.
• Note:
• Only whole tablets should be used for dosing. a Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions ( 7 ), Clinical Pharmacology ( 12.3 )]. b Drugs that induce lamotrigine glucuronidation and increase clearance, other than the specified AEDs, include estrogen-containing oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir.
• Dosing recommendations for estrogen-containing products, including oral contraceptives, and the protease inhibitor atazanavir/ritonavir, can be found in General Dosing Considerations [see Dosage and Administration ( 2.1 )].
• Patients on rifampin and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with AEDs that induce glucuronidation and increase clearance [see Dosage and Administration ( 2.1 ), Drug Interactions ( 7), Clinical Pharmacology ( 12.3 )].
• Table 3.
• The Initial Weight-Based Dosing Guide for Patients Aged 2 to 12 Years Taking Valproate (Weeks 1 to 4) with Epilepsy If the patient’s weight is Give this daily dose , using the most appropriate combination of lamotrigine 2 - and 5 - mg tablets Greater than And less than Weeks 1 and 2 Weeks 3 and 4 6.7 kg 14 kg 2 mg every other day 2 mg every day 14.1 kg 27 kg 2 mg every day 4 mg every day 27.1 kg 34 kg 4 mg every day 8 mg every day 34.1 kg 40 kg 5 mg every day 10 mg every day Usual Adjunctive Maintenance Dose for Epilepsy The usual maintenance doses identified in Tables 1 and 2 are derived from dosing regimens employed in the placebo-controlled adjunctive trials in which the efficacy of SUBVENITE was established.
• In patients receiving multidrug regimens employing carbamazepine, phenytoin, phenobarbital, or primidone without valproate , maintenance doses of adjunctive SUBVENITE as high as 700 mg/day have been used.
• In patients receiving valproate alone , maintenance doses of adjunctive SUBVENITE as high as 200 mg/day have been used.
• The advantage of using doses above those recommended in Tables 1 to 4 has not been established in controlled trials.
• 2.3 Epilepsy-Conversion from Adjunctive Therapy to Monotherapy The goal of the transition regimen is to attempt to maintain seizure control while mitigating the risk of serious rash associated with the rapid titration of SUBVENITE.
• The recommended maintenance dose of SUBVENITE as monotherapy is 500 mg/day given in 2 divided doses.
• To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations for SUBVENITE should not be exceeded [see Boxed Warning ] .
• Conversion from Adjunctive Therapy with Carbamazepine, Phenytoin, Phenobarbital, or Primidone to Monotherapy with SUBVENITE After achieving a dose of 500 mg/day of SUBVENITE using the guidelines in Table 1, the concomitant enzyme-inducing AED should be withdrawn by 20% decrements each week over a 4-week period.
• The regimen for the withdrawal of the concomitant AED is based on experience gained in the controlled monotherapy clinical trial.
• Conversion from Adjunctive Therapy with Valproate to Monotherapy with SUBVENITE The conversion regimen involves the 4 steps outlined in Table 4.
• Table 4.
• Conversion from Adjunctive Therapy with Valproate to Monotherapy with SUBVENITE in Patients Aged 16 Years and Older with Epilepsy SUBVENITE Valproate Step 1 Achieve a dose of 200 mg/day according to guidelines in Table 1.
• Maintain established stable dose.
• Step 2 Maintain at 200 mg/day.
• Decrease dose by decrements no greater than 500 mg/day/week to 500 mg/day and then maintain for 1 week.
• Step 3 Increase to 300 mg/day and maintain for 1 week.
• Simultaneously decrease to 250 mg/day and maintain for 1 week.
• Step 4 Increase by 100 mg/day every week to achieve maintenance dose of 500 mg/day.
• Discontinue.
• Conversion from Adjunctive Therapy with Antiepileptic Drugs other than Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Valproate to Monotherapy with SUBVENITE No specific dosing guidelines can be provided for conversion to monotherapy with SUBVENITE with AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate.
• 2.4 Bipolar Disorder The goal of maintenance treatment with SUBVENITE is to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy [see Indications and Usage ( 1.2 )] .
• Patients taking SUBVENITE for more than 16 weeks should be periodically reassessed to determine the need for maintenance treatment.
• Adults The target dose of SUBVENITE is 200 mg/day (100 mg/day in patients taking valproate, which decreases the apparent clearance of lamotrigine, and 400 mg/day in patients not taking valproate and taking either carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitor lopinavir/ritonavir that increase the apparent clearance of lamotrigine).
• In the clinical trials, doses up to 400 mg/day as monotherapy were evaluated; however, no additional benefit was seen at 400 mg/day compared with 200 mg/day [see Clinical Studies ( 14.2 )] .
• Accordingly, doses above 200 mg/day are not recommended.
• Treatment with SUBVENITE is introduced, based on concurrent medications, according to the regimen outlined in Table 5.
• If other psychotropic medications are withdrawn following stabilization, the dose of SUBVENITE should be adjusted.
• In patients discontinuing valproate, the dose of SUBVENITE should be doubled over a 2-week period in equal weekly increments (see Table 6).
• In patients discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation, the dose of SUBVENITE should remain constant for the first week and then should be decreased by half over a 2-week period in equal weekly decrements (see Table 6).
• The dose of SUBVENITE may then be further adjusted to the target dose (200 mg) as clinically indicated.
• If other drugs are subsequently introduced, the dose of SUBVENITE may need to be adjusted.
• In particular, the introduction of valproate requires reduction in the dose of SUBVENITE [see Drug Interactions ( 7 ), Clinical Pharmacology ( 12.3 )].
• To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations of SUBVENITE should not be exceeded [see Boxed Warning ] .
• Table 5.
• Escalation Regimen for SUBVENITE in
• Adults with Bipolar Disorder In Patients TAKING Valproate a In Patients NOT TAKING Carbamazepine , Phenytoin , Phenobarbital , Primidone b , or Valproate a In Patients TAKING Carbamazepine , Phenytoin , Phenobarbital , or Primidone b and NOT TAKING Valproate a Weeks 1 and 2 25 mg every other day 25 mg daily 50 mg daily Weeks 3 and 4 25 mg daily 50 mg daily 100 mg daily, in divided doses Week 5 50 mg daily 100 mg daily 200 mg daily, in divided doses Week 6 100 mg daily 200 mg daily 300 mg daily, in divided doses Week 7 100 mg daily 200 mg daily up to 400 mg daily, in divided doses a Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions ( 7 ), Clinical Pharmacology ( 12.3 )]. b Drugs that induce lamotrigine glucuronidation and increase clearance, other than the specified AEDs, include estrogen-containing products, including oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir.
• Dosing recommendations for oral contraceptives and the protease inhibitor atazanavir/ritonavir can be found in General Dosing Considerations [see Dosage and Administration ( 2.1 )] .
• Patients on rifampin and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with AEDs that induce glucuronidation and increase clearance [see Dosage and Administration ( 2.1 ), Drug Interactions (7), Clinical Pharmacology ( 12.3 )] Table 6.
• Dosage Adjustments to SUBVENITE in
• Adults with Bipolar Disorder following Discontinuation of Psychotropic Medications Discontinuation of Psychotropic Drugs ( excluding Valproate a , Carbamazepine , Phenytoin , Phenobarbital , or Primidone b ) After Discontinuation of Valproate a After Discontinuation of Carbamazepine , Phenytoin , Phenobarbital , or Primidone b Current Dose of SUBVENITE ( mg / day ) 100 Current Dose of SUBVENITE ( mg / day ) 400 Week 1 Maintain current dose of SUBVENITE 150 400 Week 2 Maintain current dose of SUBVENITE 200 300 Week 3 onward Maintain current dose of SUBVENITE 200 200 a Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions ( 7 ), Clinical Pharmacology ( 12.3 )]. b Drugs that induce lamotrigine glucuronidation and increase clearance, other than the specified AEDs, include estrogen-containing products, including oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir.
• Dosing recommendations for oral contraceptives and the protease inhibitor atazanavir/ritonavir can be found in General Dosing Considerations [see Dosage and Administration ( 2.1 )] .
• Patients on rifampin and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with AEDs that induce glucuronidation and increase clearance [see Dosage and Administration ( 2.1 ), Drug Interactions (7), Clinical Pharmacology ( 12.3 )]

Quoted from the official label, section “Dosage & Administration”.

Other warnings

Quoted from the official label, section “Warnings”.

Pregnancy and breastfeeding

Quoted from the official label, section “OTC — Pregnancy or Breast Feeding”.

Other medicines

Quoted from the official label, section “Drug Interactions”.

If you take too much

In an emergency, call your local emergency number or a poison control centre.

Quoted from the official label, section “Overdosage”.

Use in children

• Epilepsy SUBVENITE is indicated as adjunctive therapy in patients aged 2 years and older for partial-onset seizures, the generalized seizures of Lennox-Gastaut syndrome, and PGTC seizures.
• Safety and efficacy of SUBVENITE used as adjunctive treatment for partial-onset seizures were not demonstrated in a small, randomized, double-blind, placebo-controlled withdrawal trial in very young pediatric patients (aged 1 to 24 months).
• SUBVENITE was associated with an increased risk for infectious adverse reactions (SUBVENITE 37%, placebo 5%), and respiratory adverse reactions (SUBVENITE 26%, placebo 5%).
• Infectious adverse reactions included bronchiolitis, bronchitis, ear infection, eye infection, otitis externa, pharyngitis, urinary tract infection, and viral infection.
• Respiratory adverse reactions included nasal congestion, cough, and apnea.
• Bipolar Disorder Safety and efficacy of SUBVENITE for the maintenance treatment of bipolar disorder were not established in a double-blind, randomized withdrawal, placebo-controlled trial that evaluated 301 pediatric patients aged 10 to 17 years with a current manic/hypomanic, depressed, or mixed mood episode as defined by DSM-IV-TR.
• In the randomized phase of the trial, adverse reactions that occurred in at least 5% of patients taking SUBVENITE (n = 87) and were twice as common compared with patients taking placebo (n = 86) were influenza (SUBVENITE 8%, placebo 2%), oropharyngeal pain (SUBVENITE 8%, placebo 2%), vomiting (SUBVENITE 6%, placebo 2%), contact dermatitis (SUBVENITE 5%, placebo 2%), upper abdominal pain (SUBVENITE 5%, placebo 1%), and suicidal ideation (SUBVENITE 5%, placebo 0%).
• Juvenile Animal Data In a juvenile animal study in which lamotrigine (oral doses of 0, 5, 15, or 30 mg/kg) was administered to young rats from postnatal day 7 to 62, decreased viability and growth were seen at the highest dose tested and long-term neurobehavioral abnormalities (decreased locomotor activity, increased reactivity, and learning deficits in animals tested as
• adults) were observed at the 2 highest doses.
• The no-effect dose for adverse developmental effects in juvenile animals is less than the human dose of 400 mg/day on a mg/m 2 basis.

Quoted from the official label, section “Pediatric Use”.

Side effects

• Epilepsy:
• Most common adverse reactions (incidence ≥10%) in
• adults were dizziness, headache, diplopia, ataxia, nausea, blurred vision, somnolence, rhinitis, pharyngitis, and rash.
• Additional adverse reactions (incidence ≥10%) reported in children included vomiting, infection, fever, accidental injury, diarrhea, abdominal pain, and tremor.
• ( 6.1 ) Bipolar disorder:
• Most common adverse reactions (incidence >5%) in
• adults were nausea, insomnia, somnolence, back pain, fatigue, rash, rhinitis, abdominal pain, and xerostomia.
• ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact OWP Pharmaceuticals Inc. at 1-800-273-6729 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
• The following serious adverse reactions are described in more detail in the Warnings and Precautions section of the labeling:
• Serious Skin Rashes [see Warnings and Precautions ( 5.1 )] Hemophagocytic Lymphohistiocytosis [see Warnings and Precautions ( 5.2 )] Multiorgan Hypersensitivity Reactions and Organ Failure [see Warnings and Precautions ( 5.3 )] Cardiac Rhythm and Conduction Abnormalities [see Warnings and Precautions ( 5.4 )] Blood Dyscrasias [see Warnings and Precautions ( 5.5 )] Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.6) ] Aseptic Meningitis [see Warnings and Precautions ( 5.7 )] Withdrawal Seizures [see Warnings and Precautions ( 5.10 )] Status Epilepticus [see Warnings and Precautions ( 5.11 )]
• 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
• Epilepsy Most Common Adverse Reactions in All Clinical Trials:
• Adjunctive Therapy in
• Adults with Epilepsy:
• The most commonly observed (≥5% for SUBVENITE and more common on drug than placebo) adverse reactions seen in association with SUBVENITE during adjunctive therapy in
• adults and not seen at an equivalent frequency among placebo-treated patients were:
• dizziness, ataxia, somnolence, headache, diplopia, blurred vision, nausea, vomiting, and rash.
• Dizziness, diplopia, ataxia, blurred vision, nausea, and vomiting were dose related.
• Dizziness, diplopia, ataxia, and blurred vision occurred more commonly in patients receiving carbamazepine with SUBVENITE than in patients receiving other AEDs with SUBVENITE.
• Clinical data suggest a higher incidence of rash, including serious rash, in patients receiving concomitant valproate than in patients not receiving valproate [see Warnings and Precautions ( 5.1 )].
• Approximately 11% of the 3,378 adult patients who received SUBVENITE as adjunctive therapy in premarketing clinical trials discontinued treatment because of an adverse reaction.
• The adverse reactions most commonly associated with discontinuation were rash (3.0%), dizziness (2.8%), and headache (2.5%).
• In a dose-response trial in
• adults, the rate of discontinuation of SUBVENITE for dizziness, ataxia, diplopia, blurred vision, nausea, and vomiting was dose related.
• Monotherapy in
• Adults with Epilepsy:
• The most commonly observed (≥5% for SUBVENITE and more common on drug than placebo) adverse reactions seen in association with the use of SUBVENITE during the monotherapy phase of the controlled trial in
• adults not seen at an equivalent rate in the control group were vomiting, coordination abnormality, dyspepsia, nausea, dizziness, rhinitis, anxiety, insomnia, infection, pain, weight decrease, chest pain, and dysmenorrhea.
• The most commonly observed (≥5% for SUBVENITE and more common on drug than placebo) adverse reactions associated with the use of SUBVENITE during the conversion to monotherapy (add-on) period, not seen at an equivalent frequency among low-dose valproate-treated patients, were dizziness, headache, nausea, asthenia, coordination abnormality, vomiting, rash, somnolence, diplopia, ataxia, accidental injury, tremor, blurred vision, insomnia, nystagmus, diarrhea, lymphadenopathy, pruritus, and sinusitis.
• Approximately 10% of the 420 adult patients who received SUBVENITE as monotherapy in premarketing clinical trials discontinued treatment because of an adverse reaction.
• The adverse reactions most commonly associated with discontinuation were rash (4.5%), headache (3.1%), and asthenia (2.4%).
• Adjunctive Therapy in Pediatric Patients with Epilepsy:
• The most commonly observed (≥5% for SUBVENITE and more common on drug than placebo) adverse reactions seen in association with the use of SUBVENITE as adjunctive treatment in pediatric patients aged 2 to 16 years and not seen at an equivalent rate in the control group were infection, vomiting, rash, fever, somnolence, accidental injury, dizziness, diarrhea, abdominal pain, nausea, ataxia, tremor, asthenia, bronchitis, flu syndrome, and diplopia.
• In 339 patients aged 2 to 16 years with partial-onset seizures or generalized seizures of Lennox-Gastaut syndrome, 4.2% of patients on SUBVENITE and 2.9% of patients on placebo discontinued due to adverse reactions.
• The most commonly reported adverse reaction that led to discontinuation of SUBVENITE was rash.
• Approximately 11.5% of the 1,081 pediatric patients aged 2 to 16 years who received SUBVENITE as adjunctive therapy in premarketing clinical trials discontinued treatment because of an adverse reaction.
• The adverse reactions most commonly associated with discontinuation were rash (4.4%), reaction aggravated (1.7%), and ataxia (0.6%).
• Controlled Adjunctive Clinical Trials in
• Adults with Epilepsy:
• Table 8 lists adverse reactions that occurred in adult patients with epilepsy treated with SUBVENITE in placebo-controlled trials.
• In these trials, either SUBVENITE or placebo was added to the patient's current AED therapy.
• Table 8.
• Adverse Reactions in Pooled, Placebo-Controlled Adjunctive Trials in Adult Patients with Epilepsy a , b a Adverse reactions that occurred in at least 2% of patients treated with SUBVENITE and at a greater incidence than placebo. b Patients in these adjunctive trials were receiving 1 to 3 of the concomitant AEDs carbamazepine, phenytoin, phenobarbital, or primidone in addition to SUBVENITE or placebo.
• Patients may have reported multiple adverse reactions during the trial or at discontinuation; thus, patients may be included in more than 1 category.
• Body System / Adverse Reaction Percent of Patients Receiving Adjunctive SUBVENITE ( n = 711 ) Percent of Patients Receiving Adjunctive Placebo ( n = 419 ) Body as a whole Headache Flu syndrome Fever Abdominal pain Neck pain Reaction aggravated (seizure exacerbation) 29 7 6 5 2 2 19 6 4 4 1 1 Digestive Nausea Vomiting Diarrhea Dyspepsia Constipation Anorexia 19 9 6 5 4 2 10 4 4 2 3 1 Musculoskeletal Arthralgia 2 0 Nervous Dizziness Ataxia Somnolence Incoordination Insomnia Tremor Depression Anxiety Convulsion Irritability Speech disorder Concentration disturbance 38 22 14 6 6 4 4 4 3 3 3 2 13 6 7 2 2 1 3 3 1 2 0 1 Respiratory Rhinitis Pharyngitis Cough increased 14 10 8 9 9 6 Skin and appendages Rash Pruritus 10 3 5 2 Special senses Diplopia Blurred vision Vision abnormality 28 16 3 7 5 1 Urogenital Female patients only Dysmenorrhea Vaginitis Amenorrhea (n = 365) 7 4 2 (n = 207) 6 1 1 In a randomized, parallel trial comparing placebo with 300 and 500 mg/day of SUBVENITE, some of the more common drug-related adverse reactions were dose related (see Table 9).
• Table 9.
• Dose-Related Adverse Reactions from a Randomized, Placebo-Controlled, Adjunctive Trial in
• Adults with Epilepsy a Significantly greater than placebo group ( P <0.05). b Significantly greater than group receiving SUBVENITE 300 mg ( P <0.05).
• Percent of Patients Experiencing Adverse Reactions Adverse Reaction Placebo ( n = 73 ) SUBVENITE 300 mg ( n = 71 ) SUBVENITE 500 mg ( n = 72 ) Ataxia Blurred vision Diplopia Dizziness Nausea Vomiting 10 10 8 27 11 4 10 11 24 a 31 18 11 28 a , b 25 a , b 49 a , b 54 a , b 25 a 18 a The overall adverse reaction profile for SUBVENITE was similar between females and males and was independent of age.
• Because the largest non-Caucasian racial subgroup was only 6% of patients exposed to SUBVENITE in placebo-controlled trials, there are insufficient data to support a statement regarding the distribution of adverse reaction reports by race.
• Generally, females receiving either SUBVENITE as adjunctive therapy or placebo were more likely to report adverse reactions than males.
• The only adverse reaction for which the reports on SUBVENITE were > 10% more frequent in females than males (without a corresponding difference by gender on placebo) was dizziness (difference = 16.5%).
• There was little difference between females and males in the rates of discontinuation of SUBVENITE for individual adverse reactions.
• Controlled Monotherapy Trial in
• Adults with Partial-Onset Seizures:
• Table 10 lists adverse reactions that occurred in patients with epilepsy treated with monotherapy with SUBVENITE in a double-blind trial following discontinuation of either concomitant carbamazepine or phenytoin not seen at an equivalent frequency in the control group.
• Table 10.
• Adverse Reactions in a Controlled Monotherapy Trial in Adult Patients with Partial-Onset Seizures a , b a Adverse reactions that occurred in at least 5% of patients treated with SUBVENITE and at a greater incidence than valproate-treated patients. b Patients in this trial were converted to SUBVENITE or valproate monotherapy from adjunctive therapy with carbamazepine or phenytoin.
• Patients may have reported multiple adverse reactions during the trial; thus, patients may be included in more than 1 category. c Up to 500 mg/day. d 1,000 mg/day.
• Body System / Adverse Reaction Percent of Patients Receiving SUBVENITE c as Monotherapy ( n = 43 ) Percent of Patients Receiving Low - Dose Valproate d Monotherapy ( n = 44 ) Body as a whole Pain Infection Chest pain 5 5 5 0 2 2 Digestive Vomiting Dyspepsia Nausea 9 7 7 0 2 2 Metabolic and nutritional Weight decrease 5 2 Nervous Coordination abnormality Dizziness Anxiety Insomnia 7 7 5 5 0 0 0 2 Respiratory Rhinitis 7 2 Urogenital (female patients only) Dysmenorrhea (n = 21) 5 (n = 28) 0 Adverse reactions that occurred with a frequency of < 5% and > 2% of patients receiving SUBVENITE and numerically more frequent than placebo were:
• Body as a Whole:
• Asthenia, fever.
• Digestive: Anorexia, dry mouth, rectal hemorrhage, peptic ulcer.
• Metabolic and Nutritional: Peripheral edema.
• Nervous System:
• Amnesia, ataxia, depression, hypesthesia, libido increase, decreased reflexes, increased reflexes, nystagmus, irritability, suicidal ideation.
• Respiratory: Epistaxis, bronchitis, dyspnea.
• Skin and Appendages: Contact dermatitis, dry skin, sweating.
• Special Senses: Vision abnormality.
• Incidence in Controlled Adjunctive Trials in Pediatric Patients with Epilepsy:
• Table 11 lists adverse reactions that occurred in 339 pediatric patients with partial-onset seizures or generalized seizures of Lennox-Gastaut syndrome who received SUBVENITE up to 15 mg/kg/day or a maximum of 750 mg/day.
• Table 11.
• Adverse Reactions in Pooled, Placebo-Controlled Adjunctive Trials in Pediatric Patients with Epilepsy a a Adverse reactions that occurred in at least 2% of patients treated with SUBVENITE and at a greater incidence than placebo.
• Body System / Adverse Reaction Percent of Patients Receiving SUBVENITE ( n = 168 ) Percent of Patients Receiving Placebo ( n = 171 ) Body as a whole Infection Fever Accidental injury Abdominal pain Asthenia Flu syndrome Pain Facial edema Photosensitivity 20 15 14 10 8 7 5 2 2 17 14 12 5 4 6 4 1 0 Cardiovascular Hemorrhage 2 1 Digestive Vomiting Diarrhea Nausea Constipation Dyspepsia 20 11 10 4 2 16 9 2 2 1 Hemic and lymphatic Lymphadenopathy 2 1 Metabolic and nutritional Edema 2 0 Nervous system Somnolence Dizziness Ataxia Tremor Emotional lability Gait abnormality Thinking abnormality Convulsions Nervousness Vertigo 17 14 11 10 4 4 3 2 2 2 15 4 3 1 2 2 2 1 1 1 Respiratory Pharyngitis Bronchitis Increased cough Sinusitis Bronchospasm 14 7 7 2 2 11 5 6 1 1 Skin Rash Eczema Pruritus 14 2 2 12 1 1 Special senses Diplopia Blurred vision Visual abnormality 5 4 2 1 1 0 Urogenital Male and female patients Urinary tract infection 3 0 Bipolar Disorder in
• Adults The most common adverse reactions seen in association with the use of SUBVENITE as monotherapy (100 to 400 mg/day) in adult patients (aged 18 to 82 years) with bipolar disorder in the 2 double-blind, placebo-controlled trials of 18 months' duration are included in Table 12.
• Adverse reactions that occurred in at least 5% of patients and were numerically more frequent during the dose-escalation phase of SUBVENITE in these trials (when patients may have been receiving concomitant medications) compared with the monotherapy phase were:
• headache (25%), rash (11%), dizziness (10%), diarrhea (8%), dream abnormality (6%), and pruritus (6%).
• During the monotherapy phase of the double-blind, placebo-controlled trials of 18 months' duration, 13% of 227 patients who received SUBVENITE (100 to 400 mg/day), 16% of 190 patients who received placebo, and 23% of 166 patients who received lithium discontinued therapy because of an adverse reaction.
• The adverse reactions that most commonly led to discontinuation of SUBVENITE were rash (3%) and mania/hypomania/mixed mood adverse reactions (2%).
• Approximately 16% of 2,401 patients who received SUBVENITE (50 to 500 mg/day) for bipolar disorder in premarketing trials discontinued therapy because of an adverse reaction, most commonly due to rash (5%) and mania/hypomania/mixed mood adverse reactions (2%).
• The overall adverse reaction profile for SUBVENITE was similar between females and males, between elderly and nonelderly patients, and among racial groups.
• Table 12.
• Adverse Reactions in 2 Placebo-Controlled Trials in Adult Patients with Bipolar I Disorder a , b Body System / Adverse Reaction Percent of Patients Receiving SUBVENITE ( n = 227 ) Percent of Patients Receiving Placebo ( n = 190 ) General Back pain Fatigue Abdominal pain 8 8 6 6 5 3 Digestive Nausea Constipation Vomiting 14 5 5 11 2 2 Nervous System Insomnia Somnolence Xerostomia (dry mouth) 10 9 6 6 7 4 Respiratory Rhinitis Exacerbation of cough Pharyngitis 7 5 5 4 3 4 Skin Rash (nonserious) c 7 5 a Adverse reactions that occurred in at least 5% of patients treated with SUBVENITE and at a greater incidence than placebo. b Patients in these trials were converted to SUBVENITE (100 to 400 mg/day) or placebo monotherapy from add-on therapy with other psychotropic medications.
• Patients may have reported multiple adverse reactions during the trial; thus, patients may be included in more than 1 category. c In the overall bipolar and other mood disorders clinical trials, the rate of serious rash was 0.08% (1 of 1,233) of adult patients who received SUBVENITE as initial monotherapy and 0.13% (2 of 1,538) of adult patients who received SUBVENITE as adjunctive therapy [see Warnings and Precautions ( 5.1 )].
• Other reactions that occurred in 5% or more patients but equally or more frequently in the placebo group included:
• dizziness, mania, headache, infection, influenza, pain, accidental injury, diarrhea, and dyspepsia.
• Adverse reactions that occurred with a frequency of <5% and >1% of patients receiving SUBVENITE and numerically more frequent than placebo were:
• General:
• Fever, neck pain.
• Cardiovascular: Migraine.
• Digestive: Flatulence.
• Metabolic and Nutritional: Weight gain, edema.
• Musculoskeletal: Arthralgia, myalgia.
• Nervous System:
• Amnesia, depression, agitation, emotional lability, dyspraxia, abnormal thoughts, dream abnormality, hypoesthesia.
• Respiratory: Sinusitis.
• Urogenital: Urinary frequency.
• Adverse Reactions following Abrupt Discontinuation:
• In the 2 controlled clinical trials, there was no increase in the incidence, severity, or type of adverse reactions in patients with bipolar disorder after abruptly terminating therapy with SUBVENITE.
• In the clinical development program in
• adults with bipolar disorder, 2 patients experienced seizures shortly after abrupt withdrawal of SUBVENITE [see Warnings and Precautions ( 5.10 )].
• Mania/Hypomania/Mixed Episodes:
• During the double-blind, placebo-controlled clinical trials in bipolar I disorder in which
• adults were converted to monotherapy with SUBVENITE (100 to 400 mg/day) from other psychotropic medications and followed for up to 18 months, the rates of manic or hypomanic or mixed mood episodes reported as adverse reactions were 5% for patients treated with SUBVENITE (n = 227), 4% for patients treated with lithium (n = 166), and 7% for patients treated with placebo (n = 190).
• In all bipolar controlled trials combined, adverse reactions of mania (including hypomania and mixed mood episodes) were reported in 5% of patients treated with SUBVENITE (n = 956), 3% of patients treated with lithium (n = 280), and 4% of patients treated with placebo (n = 803).
• 6.2 Other Adverse Reactions Observed in All Clinical Trials SUBVENITE has been administered to 6,694 individuals for whom complete adverse reaction data was captured during all clinical trials, only some of which were placebo controlled.
• During these trials, all adverse reactions were recorded by the clinical investigators using terminology of their own choosing.
• To provide a meaningful estimate of the proportion of individuals having adverse reactions, similar types of adverse reactions were grouped into a smaller number of standardized categories using modified COSTART dictionary terminology.
• The frequencies presented represent the proportion of the 6,694 individuals exposed to SUBVENITE who experienced an event of the type cited on at least 1 occasion while receiving SUBVENITE.
• All reported adverse reactions are included except those already listed in the previous tables or elsewhere in the labeling, those too general to be informative, and those not reasonably associated with the use of the drug.
• Adverse reactions are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions:
• frequent adverse reactions are defined as those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1,000 patients; rare adverse reactions are those occurring in fewer than 1/1,000 patients.
• Body as a Whole Infrequent: Allergic reaction, chills, malaise.
• Cardiovascular System Infrequent:
• Flushing, hot flashes, hypertension, palpitations, postural hypotension, syncope, tachycardia, vasodilation.
• Dermatological Infrequent:
• Acne, alopecia, hirsutism, maculopapular rash, skin discoloration, urticaria.
• Rare:
• Angioedema, erythema, exfoliative dermatitis, fungal dermatitis, herpes zoster, leukoderma, multiforme erythema, petechial rash, pustular rash, Stevens-Johnson syndrome, vesiculobullous rash.
• Digestive System Infrequent:
• Dysphagia, eructation, gastritis, gingivitis, increased appetite, increased salivation, liver function tests abnormal, mouth ulceration.
• Rare:
• Gastrointestinal hemorrhage, glossitis, gum hemorrhage, gum hyperplasia, hematemesis, hemorrhagic colitis, hepatitis, melena, stomach ulcer, stomatitis, tongue edema.
• Endocrine System Rare: Goiter, hypothyroidism.
• Hematologic and Lymphatic System Infrequent: Ecchymosis, leukopenia.
• Rare:
• Anemia, eosinophilia, fibrin decrease, fibrinogen decrease, iron deficiency anemia, leukocytosis, lymphocytosis, macrocytic anemia, petechia, thrombocytopenia.
• Metabolic and Nutritional Disorders Infrequent: Aspartate transaminase increased.
• Rare:
• Alcohol intolerance, alkaline phosphatase increase, alanine transaminase increase, bilirubinemia, general edema, gamma glutamyl transpeptidase increase, hyperglycemia.
• Musculoskeletal System Infrequent : Arthritis, leg cramps, myasthenia, twitching.
• Rare: Bursitis, muscle atrophy, pathological fracture, tendinous contracture.
• Nervous System Frequent: Confusion, paresthesia.
• Infrequent:
• Akathisia, apathy, aphasia, central nervous system depression, depersonalization, dysarthria, dyskinesia, euphoria, hallucinations, hostility, hyperkinesia, hypertonia, libido decreased, memory decrease, mind racing, movement disorder, myoclonus, panic attack, paranoid reaction, personality disorder, psychosis, sleep disorder, stupor, suicidal ideation.
• Rare:
• Choreoathetosis, delirium, delusions, dysphoria, dystonia, extrapyramidal syndrome, faintness, grand mal convulsions, hemiplegia, hyperalgesia, hyperesthesia, hypokinesia, hypotonia, manic depression reaction, muscle spasm, neuralgia, neurosis, paralysis, peripheral neuritis.
• Respiratory System Infrequent: Yawn.
• Rare: Hiccup, hyperventilation.
• Special Senses Frequent: Amblyopia.
• Infrequent:
• Abnormality of accommodation, conjunctivitis, dry eyes, ear pain, photophobia, taste perversion, tinnitus.
• Rare:
• Deafness, lacrimation disorder, oscillopsia, parosmia, ptosis, strabismus, taste loss, uveitis, visual field defect.
• Urogenital System Infrequent:
• Abnormal ejaculation, hematuria, impotence, menorrhagia, polyuria, urinary incontinence.
• Rare:
• Acute kidney failure, anorgasmia, breast abscess, breast neoplasm, creatinine increase, cystitis, dysuria, epididymitis, female lactation, kidney failure, kidney pain, nocturia, urinary retention, urinary urgency.
• 6.3 Postmarketing Experience The following adverse reactions have been identified during postapproval use of SUBVENITE.
• Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
• Blood and Lymphatic Agranulocytosis, hemolytic anemia, lymphadenopathy not associated with hypersensitivity disorder, pseudolymphoma.
• Gastrointestinal Esophagitis.
• Hepatobiliary Tract and Pancreas Pancreatitis.
• Immunologic Hypogammaglobulinemia, lupus-like reaction, vasculitis.
• Lower Respiratory Apnea.
• Musculoskeletal Rhabdomyolysis has been observed in patients experiencing hypersensitivity reactions.
• Nervous System Aggression, exacerbation of Parkinsonian symptoms in patients with pre-existing Parkinson's disease, tics.
• Non-site Specific Progressive immunosuppression.
• Renal and Urinary Disorders Tubulointerstitial nephritis (has been reported alone and in association with uveitis).
• Skin and Subcutaneous Tissue Disorders Photosensitivity reaction.

Quoted from the official label, section “Adverse Reactions”.

What to discuss with your doctor

• Advise the patient to read the FDA-approved patient labeling (Medication Guide).
• Rash Prior to initiation of treatment with SUBVENITE, inform patients that a rash or other signs or symptoms of hypersensitivity (e.g., fever, lymphadenopathy) may herald a serious medical event and instruct them to report any such occurrence to their healthcare providers immediately.
• Hemophagocytic Lymphohistiocytosis Prior to initiation of treatment with SUBVENITE, inform patients that excessive immune activation may occur with SUBVENITE and that they should report signs or symptoms such as fever, rash, or lymphadenopathy to a healthcare provider immediately.
• Multiorgan Hypersensitivity Reactions, Blood Dyscrasias, and Organ Failure Inform patients that multiorgan hypersensitivity reactions and acute multiorgan failure may occur with SUBVENITE.
• Isolated organ failure or isolated blood dyscrasias without evidence of multiorgan hypersensitivity may also occur.
• Instruct patients to contact their healthcare providers immediately if they experience any signs or symptoms of these conditions [see Warnings and Precautions ( 5.3 , 5.5 )] .
• Cardiac Rhythm and Conduction Abnormalities Inform patients that, due to its mechanism of action, SUBVENITE could lead to irregular or slowed heart rhythm.
• This risk is increased in patients with underlying cardiac disease or heart conduction problems or who are taking other medications that affect heart conduction.
• Patients should be made aware of and report cardiac signs or symptoms to their healthcare provider right away.
• Patients who develop syncope should lie down with raised legs and contact their healthcare provider [see Warnings and Precautions ( 5.4 )] .
• Suicidal Thinking and Behavior Inform patients, their caregivers, and families that AEDs, including SUBVENITE, may increase the risk of suicidal thoughts and behavior.
• Instruct them to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior or thoughts about self-harm.
• Instruct them to immediately report behaviors of concern to their healthcare providers.
• Worsening of Seizures Instruct patients to notify their healthcare providers if worsening of seizure control occurs.
• Central Nervous System Adverse Effects Inform patients that SUBVENITE may cause dizziness, somnolence, and other symptoms and signs of central nervous system depression.
• Accordingly, instruct them neither to drive a car nor to operate other complex machinery until they have gained sufficient experience on SUBVENITE to gauge whether or not it adversely affects their mental and/or motor performance.
• Pregnancy and Nursing Instruct patients to notify their healthcare providers if they become pregnant or intend to become pregnant during therapy and if they intend to breastfeed or are breastfeeding an infant.
• Encourage patients to enroll in the NAAED Pregnancy Registry if they become pregnant.
• This registry is collecting information about the safety of AEDs during pregnancy.
• To enroll, patients can call the toll-free number 1-888-233-2334 [see Use in Specific Populations ( 8.1 )] .
• Inform patients who intend to breastfeed that SUBVENITE is present in breast milk and advise them to monitor their child for potential adverse effects of this drug.
• Discuss the benefits and risks of continuing breastfeeding.
• Use of Estrogen-Containing Products, Including Oral Contraceptives Instruct women to notify their healthcare providers if they plan to start or
• stop use of oral contraceptives or other female hormonal preparations (including HRT).
• Starting estrogen-containing products, including oral contraceptives, may significantly decrease lamotrigine plasma levels, and stopping estrogen-containing oral contraceptives (including the pill-free week) may significantly increase lamotrigine plasma levels [see Warnings and Precautions ( 5.9 ), Clinical Pharmacology ( 12.3 )] .
• Also instruct women to promptly notify their healthcare providers if they experience adverse reactions or changes in menstrual pattern (e.g., break-through bleeding) while receiving SUBVENITE in combination with these medications.
• Discontinuing SUBVENITE Instruct patients to notify their healthcare providers if they stop taking SUBVENITE for any reason and not to resume SUBVENITE without consulting their healthcare providers.
• Aseptic Meningitis Inform patients that SUBVENITE may cause aseptic meningitis.
• Instruct them to notify their healthcare providers immediately if they develop signs and symptoms of meningitis such as headache, fever, nausea, vomiting, stiff neck, rash, abnormal sensitivity to light, myalgia, chills, confusion, or drowsiness while taking SUBVENITE.
• Potential Medication Errors To
• avoid a medication error of using the wrong drug or formulation, strongly advise patients to visually inspect their tablets to verify that they are SUBVENITE, as well as the correct formulation of lamotrigine, each time they fill their prescription [see Dosage Forms and Strengths ( 3.1 ), How Supplied/Storage and Handling ( 16 )] .
• Refer the patient to the Medication Guide that provides depictions of the SUBVENITE tablets.
• The brands listed are trademarks of their respective owners.

Quoted from the official label, section “Patient Counseling Information”.

Strengths and forms

• FORMS AND STRENGTHS Tablets: 25 mg, 100 mg, 150 mg, and 200 mg; scored.
• ( 3.1 , 16 )
• 3.1 Tablets 25 mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with "2L" on one side and break line on other side. 100 mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with "10LA" on one side and break line on other side. 150 mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with "15LA" on one side and break line on other side. 200 mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with "20LA" on one side and break line on other side.

Quoted from the official label, section “Dosage Forms & Strengths”.

What it looks like and how it is packed

• SUBVENITE (lamotrigine) tablets, USP 25 mg White to off white, round shape, flat face beveled edge, uncoated tablets debossed with “2L” on one side and break line on other side.
• Bottle of 100 NDC-69102-301-01 Bottle of 6600 NDC-69102-301-02 SUBVENITE (lamotrigine) tablets, USP 100 mg White to off white, round shape, flat face beveled edge, uncoated tablets debossed with “10LA” on one side and break line on other side.
• Bottle of 100 NDC-69102-319-01 Bottle of 2500 NDC-69102-319-02 SUBVENITE (lamotrigine) tablets, USP 150 mg White to off white, round shape, flat face beveled edge, uncoated tablets debossed with “15LA” on one side and break line on other side.
• Bottle of 100 NDC-69102-150-06 SUBVENITE (lamotrigine) tablets, USP 200 mg White to off white, round shape, flat face beveled edge, uncoated tablets debossed with “20LA” on one side and break line on other side.
• Bottle of 100 NDC-69102-320-01 SUBVENITE (lamotrigine) tablets, USP Starter Kit for Patients Not Taking Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Valproate (Orange Kit). 25-mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with “2L” on one side and break line on other side. 100-mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with “10LA” on one side and break line on other side.
• Blister pack of 42, 25 mg tablets and 7, 100 mg tablets NDC-69102-300-01 SUBVENITE (lamotrigine) tablets, USP Starter Kit for Patients Taking Carbamazepine, Phenytoin, Phenobarbital, or Primidone and Not Taking Valproate (Green Kit). 25-mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with “2L” on one side and break line on other side. 100-mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with “10LA” on one side and break line on other side.
• Blister pack of 84, 25 mg tablets and 14, 100 mg tablets NDC-69102-312-01 SUBVENITE (lamotrigine) tablets, USP Starter Kit for Patients Taking Valproate (Blue Kit). 25-mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with “2L” on one side and break line on other side.
• Blister pack of 35 tablets NDC-69102-306-01 Storage
• Store at 20° to 25° C (68° to 77° F); excursions permitted to 15° to 30° C (59° to 86° F) [See USP Controlled Room Temperature].

Quoted from the official label, section “How Supplied”.

What is in it

• Lamotrigine, USP an AED of the phenyltriazine class, is chemically unrelated to existing AEDs.
• Lamotrigine's chemical name is 3,5-diamino-6-(2,3-dichlorophenyl)- as -triazine, its molecular formula is C 9 H 7 N 5 Cl 2 , and its molecular weight is 256.09.
• Lamotrigine, USP is a white to pale cream-colored powder and has a pK a of 5.7.
• Lamotrigine, USP is very slightly soluble in water (0.17 mg/mL at 25°C) and slightly soluble in
• 0.1 M HCl (4.1 mg/mL at 25°C).
• The structural formula is:
• SUBVENITE (lamotrigine) tablets, USP are supplied for oral administration as 25-mg (white to off white), 100-mg (white to off white), 150-mg (white to off white), and 200-mg (white to off white) tablets.
• Each tablet contains the labeled amount of lamotrigine, USP and the following inactive ingredients:
• lactose monohydrate; magnesium stearate; microcrystalline cellulose; povidone; and sodium starch glycolate.
• Meets USP Dissolution Test 3 structure

Quoted from the official label, section “Description”.

Ingredients people check for

Lactose, gluten, dyes, sugars and other ingredients that matter with an allergy, intolerance or diet — as this product’s FDA label lists them.

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Details

Source: NDC Directory · 2026-09-13 · not reviewed by a clinician

Source: US Food and Drug Administration, NDC Directory. Reuse terms: US government work (FDA).

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